T-cell specific upregulation of Sema4A as risk factor for autoimmunity in systemic lupus erythematosus and rheumatoid arthritis.

Abstract

The aim of the present study was to evaluate the impact of SEMA4A genetic variants on expression of sema4A protein and its relation to autoimmunity development in Systemic Lupus Erythematosus and Rheumatoid Arthritis patients. A total of 541 SLE patients, 390 RA patients and 607 healthy individuals were genotyped. We also assessed SEMA4A mRNA expression from whole blood cells and the in vitro protein production from resting and activated T lymphocytes as well as mature dendritic cells from healthy individuals stratified according to their genotypes for SLE/RA associated SEMA4A variants. Our results showed that T/T genotype for rs3738581 SNP is associated with both RA and SLE development (p = .000053, OR = 2.35; p = .0019, OR = 2.07, respectively; statistical power = 100%) and also to an increased in vitro sema4A production in active T lymphocytes. Our findings are indicative of a T cell-specific upregulation of sema4A in the presence of T/T genotype, being a risk factor for SLE and RA.

• Authors: Catarina Addobbati Jordão Cavalcanti, Vanessa Germoglio, Jaqueline de Azevêdo Silva, Nadine Glesse, Priscila Vianna, Giovana Cechim, Odirlei Andre Monticielo, Ricardo Machado Xavier, João Carlos Tavares Brenol, Claiton Viegas Brenol, Thiago Sotero Fragoso, Alexandre Domingues Barbosa, Ângela Luiza Branco Pinto Duarte, Renê Donizeti Ribeiro Oliveira, Paulo Louzada-Júnior, Eduardo Antônio Donadi, José Artur Bogo Chies, Sergio Crovella, Paula Sandrin-Garcia
• Journal: Autoimmunity (Autoimmunity) Vol. 53 Issue 2 Pg. 65-70 (03 2020) ISSN: 1607-842X [Electronic] England
• PMID: 31876207 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• SEMA4A protein, human
• Semaphorins

Topics

• Adult
• Aged
• Arthritis, Rheumatoid (blood, genetics, immunology)
• Autoimmunity (genetics)
• Brazil
• Case-Control Studies
• Cohort Studies
• Dendritic Cells (immunology, metabolism)
• Female
• Genetic Predisposition to Disease
• Humans
• Lupus Erythematosus, Systemic (blood, genetics, immunology)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• RNA, Messenger (analysis, metabolism)
• Semaphorins (genetics, metabolism)
• T-Lymphocytes (immunology, metabolism)
• Up-Regulation